Chemokines are a growing family of chemotactic cytokines, which have been implicated to play a role in the recruitment and activation of cells (Oppenheim, J. J. et al., Ann Rev Immunol., 9 617-48, (1991), Schall, T. J., Cytokine, 3 165-183, (1991)). They are primarily responsible for the activation and recruitment of leukocytes, but not exclusively so. Further analysis of this superfamily of proteins has shown that it can be divided up into two further subfamilies of proteins. These have been termed CXC or α-chemokines, and the CC or β-chemokines based on the spacings of two conserved cysteine residues near to the amino terminus of the proteins.
To date two receptors have been identified for the CC chemokine family. The first, which is receptor primarily for MIP-1α (Macrophage inflammatory polypeptide-1α) and RANTES (Raised on Activation, Normal T-cell derived and Secreted) has been described previously (Gao, J. L. et al., J. Exp. Med., 177 1421-7 (1993), Neote, K. et al., Cell 72 415-25 (1993)). The second CC-chemokine receptor which has been recently described is for MCP-1 (monocyte chemotractant protein-1) Charo I. et al., Proc. Natl. Acad. Sci. USA 91 2752-2756 (1994). More recently, another receptor US28, expressed by the human cytomegalovirus, has been shown to be a receptor for RANTES, MIP-1α, and MCP-1 (Gao, J. L. and Murphy P. M., J. Biol. Chem. 269, 28539-28542 (1994)). All three receptors are of the seven transmembrane alpha helical segment type, and are expressed into the membranes of cells.
However there remains a need to identify hitherto undisclosed chemokine receptors and to characterise them in order to develop a more complete picture of the structure and function of chemokine receptors.